The effects of aging on the BTBR mouse model of autism spectrum disorder.

Abstract

Autism spectrum disorder (ASD) is a complex heterogeneous neurodevelopmental disorder characterized by alterations in social functioning, communicative abilities, and engagement in repetitive or restrictive behaviors. The process of aging in individuals with autism and related neurodevelopmental disorders is not well understood, despite the fact that the number of individuals with ASD aged 65 and older is projected to increase by over half a million individuals in the next 20 years. To elucidate the effects of aging in the context of a modified central nervous system, we investigated the effects of age on the BTBR T + tf/j mouse, a well characterized and widely used mouse model that displays an ASD-like phenotype. We found that a reduction in social behavior persists into old age in male BTBR T + tf/j mice. We employed quantitative proteomics to discover potential alterations in signaling systems that could regulate aging in the BTBR mice. Unbiased proteomic analysis of hippocampal and cortical tissue of BTBR mice compared to age-matched wild-type controls revealed a significant decrease in brain derived neurotrophic factor and significant increases in multiple synaptic markers (spinophilin, Synapsin I, PSD 95, NeuN), as well as distinct changes in functional pathways related to these proteins, including "Neural synaptic plasticity regulation" and "Neurotransmitter secretion regulation." Taken together, these results contribute to our understanding of the effects of aging on an ASD-like mouse model in regards to both behavior and protein alterations, though additional studies are needed to fully understand the complex interplay underlying aging in mouse models displaying an ASD-like phenotype.

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Citation

Published Version (Please cite this version)

10.3389/fnagi.2014.00225

Publication Info

Jasien, Joan M, Caitlin M Daimon, Rui Wang, Bruce K Shapiro, Bronwen Martin and Stuart Maudsley (2014). The effects of aging on the BTBR mouse model of autism spectrum disorder. Front Aging Neurosci, 6. p. 225. 10.3389/fnagi.2014.00225 Retrieved from https://hdl.handle.net/10161/12452.

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Scholars@Duke

Jasien

Joan Mary Jasien

Associate Professor of Pediatrics

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